144 research outputs found

    Cost-per-diagnosis as a metric for monitoring cost effectiveness of HIV testing programmes in low income settings in southern Africa : health economic and modelling analysis

    Get PDF
    Introduction: As prevalence of undiagnosed HIV declines, it is unclear whether testing programmes will be cost effective. To guide their HIV testing programmes,countries require appropriatemetrics that can be measured. The cost-per-diagnosisis potentially a useful metric. Methods:We simulated a series of setting-scenarios for adult HIV epidemics and ART programmes typical of settings in southern Africa using an individual-based model and projected forward from 2018 under two policies: (i) a minimum package of “core” testing (i.e. testing in pregnant women, for diagnosis of symptoms, in sex workers, and in men coming forward for circumcision) is conducted, and (ii) “core” testing as above plus “additional-testing”, for which we specify different rates of testing and various degrees to which those with HIV are more likely to test than thosewithout HIV. We also considered a plausible range of unit test costs. The aim was to assess the relationship between cost-per-diagnosisand the incremental cost-effectiveness ratio(ICER) of the additional-testingpolicy. Discount rate 3%; costs in 2018 US.Results:TherewasastronggradedrelationshipbetweenthecostperdiagnosisandtheICER.Overall,theICERwasbelowUS. Results:There was a strong graded relationship between the cost-per-diagnosisand the ICER. Overall, the ICERwas below 500 per-DALY-averted (the cost effectiveness threshold used in primary analysis) so long as thecost-per-diagnosiswas below 315.ThisthresholdcostperdiagnosiswassimilaraccordingtoepidemicandprogrammaticfeaturesincludingtheprevalenceofundiagnosedHIV,theHIVincidenceandameasureofHIVprogrammequality(theproportionofHIVdiagnosedpeoplehavingaviralload<1000copies/mL).However,restrictingtowomen,additionaltestingdidnotappearcosteffectiveevenatacostperdiagnosisofbelow315. This thresholdcost-per-diagnosiswas similar according to epidemic and programmatic features including the prevalence of undiagnosed HIV, the HIV incidence and a measure of HIV programme quality (the proportion of HIV diagnosed people having a viral load <1000 copies/mL). However, restrictingto women, additional-testingdid not appear cost-effective even at acost-per-diagnosisof below 50, while restrictingto men additional-testingwas cost effective up to a cost-per-diagnosisof 585.Thethresholdcostfortestinginmenfellto585. Thethreshold cost for testing in men fell to 256 when the cost effectiveness threshold was 300insteadof300instead of 500, and to $81 when considering a discount rate of 10% perannum.Conclusions:For testing programmesin low income settings in southern African there is an extremely strong relationship between the cost-per-diagnosisand the cost per DALY averted, indicating that the cost-per-diagnosiscan be used to monitor the cost effectiveness of testing programmes

    Exceptional Diversity, Non-Random Distribution, and Rapid Evolution of Retroelements in the B73 Maize Genome

    Get PDF
    Recent comprehensive sequence analysis of the maize genome now permits detailed discovery and description of all transposable elements (TEs) in this complex nuclear environment. Reiteratively optimized structural and homology criteria were used in the computer-assisted search for retroelements, TEs that transpose by reverse transcription of an RNA intermediate, with the final results verified by manual inspection. Retroelements were found to occupy the majority (>75%) of the nuclear genome in maize inbred B73. Unprecedented genetic diversity was discovered in the long terminal repeat (LTR) retrotransposon class of retroelements, with >400 families (>350 newly discovered) contributing >31,000 intact elements. The two other classes of retroelements, SINEs (four families) and LINEs (at least 30 families), were observed to contribute 1,991 and ∼35,000 copies, respectively, or a combined ∼1% of the B73 nuclear genome. With regard to fully intact elements, median copy numbers for all retroelement families in maize was 2 because >250 LTR retrotransposon families contained only one or two intact members that could be detected in the B73 draft sequence. The majority, perhaps all, of the investigated retroelement families exhibited non-random dispersal across the maize genome, with LINEs, SINEs, and many low-copy-number LTR retrotransposons exhibiting a bias for accumulation in gene-rich regions. In contrast, most (but not all) medium- and high-copy-number LTR retrotransposons were found to preferentially accumulate in gene-poor regions like pericentromeric heterochromatin, while a few high-copy-number families exhibited the opposite bias. Regions of the genome with the highest LTR retrotransposon density contained the lowest LTR retrotransposon diversity. These results indicate that the maize genome provides a great number of different niches for the survival and procreation of a great variety of retroelements that have evolved to differentially occupy and exploit this genomic diversity
    corecore